. Biology of Reproduction, lecture on Lactation

Biology of Reproduction

Fall 1998

text: Human Reproductive Biology 2nd Edition - R.E. Jones: Read pages 365-450 for this lecture

XXIII. Sexual Response and Behavior                          back to XXII. Lactation

	A. requires integration of multi-sensory input

		1. balanced sensory and physiological coordination	

			a. \ integration of neural control and endocrine modulation

				i. seasonal cues (e.g. light and/or To) via sensory
				    receptors must activate HPG axis ®
					follicular growth and spermatogenesis

					(1) or puberty

					(2) pulsatile GnRH & LH secretion required

				ii. +feedback is necessary for cyclicity

				iii. appropriate cycle phase means
				      appropriate ­ in hormone

				iv. ­ hormone (may be) required to prime neural
					centers for sensory information for arousal
					 and/or behavior

				v.  signal stimuli are sensory information which
				    can now activate complete circuits for arousal

				vi. sense mediated arousal must be coordinated
				     with sensory behavioral information

				vii. efferent signals stimulate endocrine
				      and motor outputs for behavior

				viii. behavioral elements (there may be many) and
				        arousal must be coordinated for successful
					    sexual response between male and female

			b. many components of sexual behavior and responsivity
			    are still unknown

				i. e.g. the role of hormones in human female sexual
				    desire is controversial

	B. Lordosis  (an example)

		1. Reflex - stimulated by tactile sensory input of male
		    body against females rump (rats)

			a. this reflex requires input from the brain

				i. input from the brain is dependent on hormone
				    priming and sensory stimulation of arousal 

		2. afferent information in fibers of anterolateral spinal columns

			a. to 3 sites: 

				i. lateral vestibular nucleus (LVN): postural control

				ii. medullary and midbrain reticular formations
				    + midbrain central gray
					(1) midbrain central gray: integrates autonomic,
					    limbic, sensory & motor information

					(2) midbrain reticular formation: brain arousal

					(3) medullary (+ pontine) reticular formations:
					    modulation of muscular reflexes

		3. E2  primes neurons of the ventromedial hypothalamus,
		     raising the level of tonic activity

			a. ­ axon terminal levels of GnRH, and up-regulates P-R

			b. GnRH potentiates neurons of the midbrain central gray 

				i. threshold facilitation necessary

		4. E2 is followed by a short burst of P
		    prior to lordosis (luteinization precedes ovulation)

			a. P: fast response - intracellular
			    and membrane receptors

			b. P inhibits 5-HT

				i. via GABAA

				ii. 5-HT tonically inhibits behavior:
				    \ P disinhibits system

		5. accessory olfactory (vomeronasal) information
		    potentiates E2/P effects

			a. olfactory/accessory olfactory neurons secrete GnRH

				i. hypothalamic GnRH develops
				    ontogenetically from olfactory tissue

			b. visual input, e.g. presence of the male,
			   also facilitates response 

		6. midbrain reticular formation (reflexive arousal)
		    + midbrain central gray (hormonal + neuromodulator
		    potentiation) neurons activate medullary reticular neurons

		7. Reflex can now be completed via medullary reticular formation 

			a. project through reticulospinal tract to ventral
			   horn motor neurons

		8. Efferent spinal neurons stimulate contraction of back muscles

			a. facilitated by LVN neurons

	C. Endocrine roles in sexual responsiveness and behavior

		1. steroid hormones primarily influence sexuality of males
		    and females by affecting sexual desire

			a. in some animals, e.g. rodents, steroids may influence
			    both the ability to engage in sex and sexual interest

				i. in nonprimate mammals orchidectomy completely
				   abolishes sexual behavior

					(1) restored by exogenous hormone

				ii. encephalization of sexual behavior hypothesis
				     (Frank Beach)

					(1) as neocortex becomes elaborated hormones
					     have less influence on sexual behavior

					(2) cortical mechanisms substitute for hormonally
					     regulated reflexive stereotypical behavior

						(a) increased flexiblity and lability of sexual
						    motivation and behavior

						(b) cortical mechanisms are modulated by hormones
						     and neurogenic steroids and peptides

							(i) GnRH, AVP/AVT, DHEA, E2
							     are made centrally

		2. hormonal effects on sexual behavior are influenced
		   strongly by social context

			a. under some circumstances hormone levels will accurately
			    predict the occurrence of sexual behavior

				i. in different social contexts the same hormonal
				     conditions will appear unrelated to  the occurrence
					 of sexual activity

				ii. e.g. ovarian cycle and  hormones are more important
				     for sexual activity in multifemale groups than
					 male-female pairs

					(1) female primates in pairs mate at any time;
					    even without ovaries

					(2) grouped females show greatest sexual 
					     behavior midcycle; no behavior at all 
						 during early follicular or luteal phases

						(a) female initiation behavior = proceptivity
						     posively correlates with [E2],
							 negatively with [P]

						(b) human females exhibit ­ libido
						     midcycle & pre- and/or post-menstrually;
							 peak coital rate on the day of greatest
							 [E2] and LH surge

						(c) adrenal androgens may be the most
						     potent stimulators of human female
							 sexual motivation

							(i) further uncoupling sexual desire
							    and activity from cyclicity

							(ii) adrenalectomy eliminates sexual interest

							(iii) adx + aromatizable androgen
							      replacement restores libido;
								  menopausal women experience
								  an ­ in sexual desire

							(iv) necessity of aromatization suggests E-R

				iii. testicular steroids are more important sexual
				      responsivity in mulitmale-multifemale groups
					  than male-female pairs

				iv. erotic arousal stimulates LH + T secretion in men

					(1) T decreases with age,
					    but not in sexually active men

		3. hormones are not strict regulators of sexual behavior

			a. castrated male humans acheive penile erection
			   in response to sexual stimulation

				i. excess androgen does not produce excessive sex drive

			b. regulate some physical aspects of sexual functioning

				i. vaginal lubrication

				ii. rigidity of erection

	D. Erection - hemotumescence (another example)

		1. vasocongestion leading to hemotumescence
		   ® arterial flow into tissue > veinous drainage 

		2. male and female

		3. spinal cord reflex

			a. erection reflex center in the sacral spinal cord

				i. erotic neural input may be direct
				    or indirect via the brain

				ii. sympathetic/parasympathetic

					(1) innervate arterioles to corpus cavernosum,
					    corpus spongiosum, labia minora

			b. erotic stimuli ® ­ parasympathetic action 

				i. release ACh

					(1) ACh colocalized with VIP

					(2) VIP also released

						(a) VIP ­ ACh secretion and effectiveness

						(b) histamine, 5-HT, substance P, adenosine,
						     and ATP may also mediate erection

				ii. sympathetic (= fight or flight) can block arousal 

			c. ACh binds to muscarinic receptors

				i. M1,3,5-R activate PLC (phospholipase C) ®
				   ­ IP3 (inositol triphosphate) ® opens endoplasmic
					 and membrane Ca++ channels

				ii. Ca++ activates NOS (nitric oxide synthase)

				iii. NOS converts Arg to Cit; giving off NO

				iv. NO diffuses to all nearby cells (smooth muscle cells)

				v. NO binds to the heme in GC (guanylate cyclase)

					(1) GC ® ­ cGMP ® relax arteriole smooth muscle

						(a) by ¯ Ca++, dephosphorylating myosin,
							  or ­ K+ ® hyperpolarizing cell

						(b) sildenafil citrate (viagra) potentiates
						     erection by inhibiting PDE5 (phosphodiesterase5);
							 PDE5 catabolizes cGMP

			d. \ NO ® arterioles dilate ® vasocongestion

			e. T, DHT enhance penile sensory feedback

				i. DHT (not aromatizable to E2) can restore
				    penile function in castrates without reinstating
				    male sexual behavior

					(1) castration eliminates erection and behavior
					     in rats, only reduces them in
						 primates (including humans)

						(a) transection of the dorsal nerve of the
						     penis eliminates erection and intromission
							 in rats, but not in primates

					(2) complete penile sensory feedback is necessary
					    for/enhances erection, intromission, ejaculation

						(a) rats without senory feedback (e.g. anesthesia)
						     mount without completing intromission
							 and ejaculation

				ii. aromatizable androgens enhance sexual behavior
				    (rats, some primates)

					(1) T ® ­ both penile function and sexual behavior

					(2) in rats aromatization blockers can eliminate
					    sexual behavior

					(3) context (read neuromodulation) strongly
					    affects the role of androgens

						(a) testicular suppression results in ¯ sexual
						      behavior fast (1 wk in rhesus monkeys)
							  in multimale groups, slower (7 wks)
							  male-female pairs

						(b) A-R blockers ¯ sexual desire and interest
						     in human males, but do not effect
							 erections in response to sexually
							 explicit material

	E. Phases of sexual response in humans

		1. excitement

			a. female

				i. vaginal lubrication (10-30 s)

				ii. vaginal barrel ­ in length & width (inner  2/3)

				iii. uterus/cervix ascends (tenting)
				     also ­ length of vagina

				iv. vasocongestion of clitoris, vagina, uterus,
				    labia minora, nipples

				v. tumescence of clitoris (corpus cavernosum and glans),
				   labia minora, nipples, and breasts (by 25%)

				vi. retraction of labia majora 

				vii. uterine contractile fibrilliation

				viii. darkening of vagina, areola;  sex flush or
				       reddening abdomen, throat, chest, face, shoulders,
					   arms, thighs (74%)

				ix. myotonia

			b. male

				i. vasocongestion ® tumescence of the penis

					(1) corpus cavernosum and corpus spongiosum

				ii. urethral meatus widens

				iii. cremaster muscle contraction elevates testes

				iv. scrotal skin becomes congested/thick;
				     nipples erect (60%)

				v. sex flush (50-60%)

				vi. ­ HR, BP, breathing

				vii. myotonia

		2. plateau

			a. female

				i. orgasmic platform = imminent orgasm: engorgment 
				     of outer 1/3 of vaginal wall,
					labia minora ® vaginal
					cavity reduced, labia become larger

				ii. clitoris retracts (¯ length 50%), covered by
				     clitoral foreskin or hood

				iii. ­ HR, BP, breathing

				iv. ­ uterine fibrillation and tenting, nipple erection,
				     breast size (maximal), darkening areola,
					 sex flush & myotonia

			b. male

				i. slight ­ in glans of the penis, darkens,
				    coronal ridge swells

				ii. urethral bulb ­ 3X 

				iii. 1st stage of ejaculation

					(1) few drops from bulbourethral gland

						(a) may contain some sperm

				iv. ­ HR, BP, breathing, myotonia, sex flush,
				     testes elevation - which rotate slightly
					 and ­ in volume (50%)

		3. orgasmic

			a. female

				i. strong muscular contractions of
				    outer 1/3 vaginal barrel

					(1) 1st contraction 2-4 s

					(2) followed by rhythmic contractions
					    at 0.8 s intervals

						(a) same frequency as male ejaculatory contractions

							(i) 3 -15 contractions typically

							(ii) status orgasmus - sustained
							      orgasm for up to 1 min

				ii. expansion of inner 2/3 of the vaginal barrel

				iii. Oxy stimulates uterine contractions

					(1) ejaculation - a small amount of fluid mostly
					    from lesser vestibular (Skene's) gland
						into the vestibule

					(2) cervical os dips

				iv. release of neuromuscular tension

			b. male

				i. loss of neuromuscular tension and voluntary control

				ii. ejaculation

					(1) ejaculation reflex

						(a) spinal cord ejaculatory center
						      (above erection center)

							(i) sympathetic neural stimulation to
							    muscles at the base of the penis

					(2) 2 phases

						(a) emmission  stage:  OXY + PGF2a ® 
							 sequential contraction of smooth muscle
							  of walls of testes, epididymis, vas deferens,
							  seminal vesicles, prostate, bulbourethral
							  gland, ejaculatory duct; and simultaneously
							  bladder sphincter

						(b) expulsion stage: rhythmic contractions
						     of bulbocavernous muscle at the base of the
							 penis ® expulsion of semen

		4. resolution

			a. female

				i. no refractory period

					(1) may return to plateau 

				ii. rapid return to normal: ceasation of vaginal
				     contractions,  clitoris leaves retracted position,
					¯ HR, BP, respiration, lightening of labia minora

				ii. cervical os dilates immediately

				iii. slower: decreased muscle tension,
				      breast & uterine size, vasocongestion of
					  clitoris, vagina and labia minora,
					  labia majora return to normal position

			b. male

				i. erection center sympathetically dominated

					(1) constricted arterioles

						(a) loss of tumescence

				ii. rapid: ¯ penis size (50%), HR, BP, respiration,
					 muscle tension, sex flush

				iii. slower: final ¯ penis size, loss of nipple
				       erection, testes/scrotal descent

XXIV. Pheromones